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Nicotinamide Riboside and NMN Enhance Regeneration of Lung Cells in 3D Culture: Preclinical Findings
Synopsis
Type 2 alveolar epithelial cells (AEC2s) are crucial for repairing and regenerating lung tissue after injury. This study found that in both idiopathic pulmonary fibrosis (IPF) patients and aged mice, these cells had low levels of a zinc transporter called ZIP8, which impaired their ability to renew and led to worsening lung scarring (fibrosis). Loss of ZIP8 disrupted SIRT1, a protein that depends on NAD+ and helps regulate cell repair and metabolism. Supplementing zinc and activating SIRT1 restored the self-renewal and differentiation of AEC2s from diseased and aged lungs. In addition, NAD-boosting molecules such as NMN and NR increased the growth of mouse AEC2s in 3D organoid culture, further supporting the idea that enhancing NAD+ pathways improves AEC2 regeneration. Mice lacking ZIP8 in these cells developed spontaneous lung fibrosis and were more vulnerable to injury. The results suggest that boosting zinc metabolism and SIRT1 activity could strengthen lung repair mechanisms and slow or prevent pulmonary fibrosis.
Journal
Journal of Clinical Investigation